M. Hoyos-Nogués et al. A Dual Molecular Biointerface Combining RGD and KRSR Sequences Improves Osteoblastic Functions by Synergizing Integrin and Cell-Membrane Proteoglycan Binding. Int. J. Mol. Sci.

M. Hoyos-Nogués, E. Falgueras-Batlle, M.P. Ginebra, J.M. Manero, J. Gil, C. Mas-Moruno. A Dual Molecular Biointerface Combining RGD and KRSR Sequences Improves Osteoblastic Functions by Synergizing Integrin and Cell-Membrane Proteoglycan Binding. Int. J. Mol. Sci. 2019, 20, 1429.

doi: 10.3390/ijms20061429

Abstract

Synergizing integrin and cell-membrane heparan sulfate proteoglycan signaling on biomaterials through peptidic sequences is known to have beneficial effects in the attachment and behavior of osteoblasts; however, controlling the exact amount and ratio of peptides tethered on a surface is challenging. Here, we present a dual molecular-based biointerface combining integrin (RGD) and heparin (KRSR)-binding peptides in a chemically controlled fashion. To this end, a tailor-made synthetic platform (PLATF) was designed and synthesized by solid-phase methodologies. The PLATF and the control linear peptides (RGD or KRSR) were covalently bound to titanium via silanization. Physicochemical characterization by means of contact angle, Raman spectroscopy and XPS proved the successful and stable grafting of the molecules. The biological potential of the biointerfaces was measured with osteoblastic (Saos-2) cells both at short and long incubation periods. Biomolecule grafting (either the PLATF, RGD or KRSR) statistically improved (p < 0.05) cell attachment, spreading, proliferation and mineralization, compared to control titanium. Moreover, the molecular PLATF biointerface synergistically enhanced mineralization (p < 0.05) of Saos-2 cells compared to RGD or KRSR alone. These results indicate that dual-function coatings may serve to improve the bioactivity of medical implants by mimicking synergistic receptor binding.